Age-related macular
degeneration (AMD) ...
is the leading cause of blindness in people over 65 years of age. In the United States alone, more than 70 million people are expected to have reached this age by the year 2050. Up to 20% of individuals older than 65 and 37% by age 75 are at risk for developing AMD. Read more
CALL FOR FUNDING APPLICATIONS:
ALERT:
The next submission date for IRRF Postdoctoral Scholar Awards is March 15, 2020. More Info.
Download form: Grant Application.doc
Questions or request for information should be forwarded to Sandra Blackwood either by phone or email.
IRRF 2017-18 BIENNIAL REPORT:
QUANTIFYING SPATIAL RELATIONSHIPS FROM WHOLE RETINAL IMAGES:
Bioinformatics, “Quantifying Spatial Relationships from Whole Retinal Images,” Brian E. Ruttenberg, Gabriel Luna, Geoffrey P. Lewis, Steven K. Fisher, and Ambuj K. Singh, NeuroscienceFOR ADDITIONAL INFORMATION OR OTHER INQUIRIES, PLEASE WRITE TO:
The International Retinal Research Foundation, Inc.
1720 University Boulevard
Birmingham, Alabama 35233
Attn: Sandra Blackwood, MPA
Executive Director
Phone: 205-325-8103
Fax: 205-325-8394
Or by email: sblackwood@irrf.org
NA3 glycan: a potential therapy for retinal pigment epithelial deficiency (SCROLL DOWN 
)
In Sumana R. Chintalapudi, XiangDi Wang; XiaoFei Wang; Yunfeng Shi, Mehmet Kocak; Mallika Palamoor; Raven N. Davis; T.J. Hollingsworth; Monica M. Jablonski.
ABSTRACT:
Atrophic age-related macular degeneration (AMD) is the most common type of AMD, yet there is no United States Food and Drug Administration (FDA)-approved therapy. This disease is characterized by retinal pigment epithelial (RPE) insufficiency, primarily in the macula, which affects the structure and physiology of photoreceptors and ultimately, visual function. In this study, we evaluated the protective effects of a naturally derived small molecule glycan therapeutic – asialo-, tri-antennary complex-type N-glycan (NA3) – in two distinct preclinical models of atrophic AMD. In RPE-deprived Xenopus laevis tadpole eyes, NA3 supported normal retinal ultrastructure. In RCS rats, NA3 supported fully functioning visual integrity.(Above: Monica Jablonski and team members in University of Tennessee – Memphis labs)
Furthermore, structural analyses revealed that NA3 prevented photoreceptor outer segment degeneration, pyknosis of the outer nuclear layer, and reactive gliosis of Müller cells (MCs). It also promoted maturation of adherens junctions between MC and photoreceptors. Our results demonstrate the neuroprotective effects of a naturally derived small molecular glycan therapeutic-NA3-in two unique preclinical models with RPE insufficiency. These data suggest that NA3 glycan therapy may provide a new therapeutic avenue in the prevention and/or treatment of retinal diseases such as atrophic AMD.
Dr. Jablonski is an IRRF-supported scientist at the University of Tennessee – Memphis.
You may access this article HERE.
RPB/IRRF Catalyst Award for Innovative Research Approaches for Age-Related Macular Degeneration (AMD)
2019 marked the fifth year of collaboration between the International Retinal Research Foundation (IRRF) and Research to Prevent Blindness (RPB) in which our collective resources were used to support focused research into the causes and possible cures for age-related macular degeneration (AMD). The American Macular Degeneration Foundation (AMDF) joined RPB and IRRF in establishing four more catalyst awards in 2019. These Catalyst Awards for Innovative Research Approaches for AMD will provide up to $300,000 per award, payable over 3 years.
THE GRANTS ARE AS FOLLOWS:
RPB/IRRF Catalyst Award for Innovative Research Approaches for AMD
Monica M. Jablonski, PhD, FARVO, Professor, University of Tennessee Health Science Center, will develop polygenetic models of AMD in order to better study disease pathogenesis and test innovative therapies.
RPB Catalyst Award for Innovative Research Approaches for AMD
Kevin L. Schey, PhD, Professor, Vanderbilt University School of Medicine, will develop a novel method of identifying early-stage AMD by correlating molecular and clinical information via a machine learning approach.
RPB/AMDF Catalyst Award for Innovative Research Approaches for AMD
Sabine Fuhrmann, PhD, Associate Professor, Vanderbilt University Medical Center will examine the potential of retinal pigment epithelium (RPE) cells to regenerate in mature mammalian eyes via specific signaling pathways.
Aparna Lakkaraju, PhD, Associate Professor, University of California, San Francisco, School of Medicine, will study RPE cell damage (a known precursor to AMD), with the goal of lerning about the mechanisms that initiate RPE damage and, subsequently, AMD.
The Catalyst Awards are aimed at researchers who are working on novel approaches to AMD research that has translational relevance or potential. A wide range of applications were considered from promoting a new understanding of AMD and to developing new treatments, including research related to both dry and wet forms of AMD. Assistant professor through full professor from any U.S. academic medical center and any relevant department were eligible to apply. However, the proposed research could not be funded – previously or at the time of application – by others, including government agencies/institutions, non-profits and private funders.
RPB and IRRF launched the first version of the Catalyst Awards in 2014, which focused on supporting novel stem cell-based approaches to AMD. In 2017, RPB and IRRF again joined together to launch the current version of the Catalyst Awards. This collaboration has been a very positive experience and the combining of our respective resources has allowed us to extend a significant award, and we feel confident that worthy recipients have again been selected. The IRRF welcomes the added participation of the American Macular Degeneration Foundation as this will further extend the impact of these awards.
About the International Retinal Research Foundation: The International Retinal Research Foundation (IRRF) provides financial support for vision research to scientists in every corner of the globe, while focusing on discovery of causes, preventions and cures of macular degeneration and diabetic retinopathy. In addition to research funding, IRRF supports training fellowships, public awareness programs, and promotes the exchange of scientific findings. To do this, IRRF must maximize every dollar. Forming partnerships and collaborations with outstanding institutions has made it possible to effectively achieve a collective impact, which will positively affect the lives of many individuals and further scientific knowledge in the vision research community. Learn more at www.irrf.org.
About Research to Prevent Blindness: Research to Prevent Blindness (RPB) is the leading nonprofit organization supporting eye research directed at the prevention, treatment, or eradication of all diseases that damage and destroy sight. RPB also supports efforts to grow and sustain a robust and diverse vision research community. RPB has awarded more than $368 million in research grants to the most talented vision scientists at the nation’s leading medical schools. As a result, RPB has been associated with nearly every major breakthrough in the understanding and treatment of vision loss in the past 59 years. Learn more at www.rpbusa.org.
About the American Macular Degeneration Foundation: The American Macular Degeneration Foundation is a patient-centered foundation that supports potentially game-changing AMD research, education and advocacy in order to improve quality of life and treatment outcomes for all those affected by AMD. Learn more at www.macular.org.
Dopamine D1 receptor activation contributes to light-adapted changes in retinal inhibition to rod bipolar cells
Michael D. Flood; Johnnie M. Moore-Dotson; and Erika D. Eggers, University of Arizona. This study was conducted with IRRF support – Erika D. Eggers. (15 AUG 2018, Vol 120, Issue 2)
ABSTRACT: Dopamine modulation of retinal signaling has been shown to be an important part of retinal adaptation to increased background light levels, but the role of dopamine modulation of retinal inhibition is not clear. This team previously showed that light adaptation causes a large reduction in inhibition to rod bipolar cells, potentially to match the decrease in excitation after rod saturation. This study determined how dopamine D1 receptors in the inner retina contribute to this modulation. It was found that D1 receptor activation significantly decreased the magnitude of inhibitory light responses from rod bipolar cells. Whereas D1 receptor blockade during light adaptation partially prevented this decline. To determine what mechanisms were involved in the modulation of inhibitory light responses, the effect of D1 receptor activation on spontaneous currents and currents evoked from electrically stimulating amacrine cell inputs to rod bipolar cells was measured. D1 receptor activation decreased the frequency of spontaneous inhibition with no change in event amplitudes, suggesting a presynaptic change in amacrine cell activity in agreement with previous reports that rod bipolar cells lack D1 receptors. Additionally, it was found that D1 receptor activation reduced the amplitude of electrically evoked responses, showing that D1 receptors can modulate amacrine cells directly. These results suggest that D1 receptor activation can replicate a large portion but not all of the effects of light adaptation, likely by modulating release from amacrine cells onto rod bipolar cells.
To access the full abstract, CLICK HERE
Erika Eggers, PhD,is an assistant professor at the University of Arizona and received IRRF funding for her study, Testing the role of dopamine as a potential treatment for diabetic retinal dysfunction.
The Eivor and Alston Callahan, MD, Endowed Chair in Ophthalmology University of Alabama at Birmingham School of Medicine
Birmingham, Al: Maria Grant, MD is the inaugural holder of the Eivor and Alston Callahan, MD Endowed Chair in Ophthalmology. Dr. Grant’s laboratory is interested in understanding the functional process of hematopoietic stem cells, and focusing on understanding how to best utilize human embryonic stem cells for vascular repair. The ability to repair vascular damage could have a profound impact on a large number of retinal diseases. The best possible approach for repair is targeted gene expression to force selective differentiation, therefore offering novel therapeutic possibilities for tissue repair throughout the body.
Dr. Grant (above) earned her medical degree from the University of Florida, where she also completed her residency. She completed a research fellowship in the Division of Endocrinology & Metabolism at the University of Florida and a research fellowship at The Wilmer Eye Institute at Johns Hopkins University.
The International Retinal Research Foundation established The Eivor and Alston Callahan, MD, Endowed Chair in Ophthalmology to support the work and mission of the Department of Ophthalmology through the recruitment and /or retention of a distinguished ophthalmologist who specializes in retina care. It is most fitting that this endowment bear the names of Dr. Alston Callahan and Mrs. Eivor Callahan, as recognition of their extraordinary legacy within the Birmingham community and the field of vision health. Dr. Callahan began the facility now known as The UAB Callahan Eye Hospital. Additionally, he was integral in the establishment of the UAB Department of Ophthalmology and served as the first Chairman.
Maria Grant, MD
EXPERIMENTAL EYE RESEARCH
Smc1 and the Cohesin Complex in Retinal Development and Disease: A New Mouse Model of Photoreceptor Degeneration
Rodrigo Martins, PhD.
Dr. Martins is an IRRF-Funded scientist at the Federal University of Rio de Janeiro, where he is an Assistant Professor. His funded project, Smc1 and the Cohesin Complex in Retinal Development and Disease: A New Mouse Model of Photoreceptor Degeneration, has resulted in a published paper in Developmental Biology, “N-myc regulates growth and fiber cell differentiation in lens development.”
Rodrigo Martins, PhD.
ABSTRACT:
Myc proto-oncogenes regulate diverse cellular processes during development, but their roles during morphogenesis of specific tissues are not fully understood. This study found that c-myc regulates cell proliferation in mouse lens development and previous genome-wide studies suggested functional roles for N-myc in developing lens. The role of N-myc was examined in mouse lens development. Genetic inaction of N-myc in the surface ectoderm or lens vesicle impaired eye and lens growth, while “late” inactivation in lens fibers had no effect. Unexpectedly, defective growth of N-myc-deficient lenses was not associated with alterations in lens progenitor cell proliferation or survival. Notably, N-myc-deficient lens exhibited a delay in degradation of DNA in terminally differentiating lens fiber cells. RNA-sequencing analysis of N-myc-deficient lenses identified a cohort of down-regulated genes associated with fiber cell differentiation that included DNaseIIβ. Further, an integrated analysis of differentially expressed genes in N-myc-deficient lens using normal lens expression patterns of iSyTE, N-myc-binding motif analysis and molecular interaction data from the String database led to the derivation of an N-myc-based gene regulatory network in the lens. Finally, analysis of N-myc and c-myc double-deficient lens demonstrated that these Myc genes cooperate to drive lens growth prior to lens vesicle stage. Together, these findings provide evidence for exclusive and cooperative functions of Myc transcription factors in mouse lens development and identify novel mechanisms by which N-myc regulates cell differentiation during eye morphogenesis.
TERMS: MYC – an immediate early response gene downstream of many ligand-membrane receptor complexes (Armelin et al., 1984; Kelly et al., 1983) binding to 10%-15% of genomic loci in mammals.
Oncogene – defined as a gene that encodes a protein that is capable of transforming cells in cultures or inducing cancer in animals.
Morphogenesis – can be defined as the processes that are responsible for producing the complex shapes of adults from the simple ball of cells that derives from division of the fertilized egg. (On-line Medical Dictionary, © 1997-98 Academic Medical Publishing & CancerWEB).
To read this paper in its entirety, please CLICK HERE.
Proceedings of the National Academy of
Sciences (PNAS) of the United States of America
Human complement factor H Y402H polymorphism causes an age-related macular degeneration phenotype and lipoprotein dysregulation in mice. Michael Landowski, Una Kelly, Mikael Klingeborn, Marybeth Groelle, Jin-Dong Ding, Daniel Grigsby and Catherine Bowes Rickman.
PNAS February 26, 2019 116 (9) 3703-3711. To read the entire article CLICK HERE.
This study was conducted with IRRF support through an RPB/IRRF Catalyst Award for Innovative Research.
SIGNIFICANCE:
The complement factor H (CFH) Y402H polymorphism (rs1061170) imparts the strongest risk for age-related macular degeneration (AMD), the leading cause of blindness in the elderly. Popular thinking holds that the CFH H402 variant increases complement activation in the eye, predisposing susceptibility to disease. However, clinical trials of complement inhibitors in AMD patients have failed. This study provides an explanation showing CFH variant-specific differences in the presentation of AMD-like pathologies. The study also shows that aged mice expressing the human H402, but not Y402 variant, (i) develop AMD-like symptoms and (ii) display differences in their systemic and ocular lipoprotein levels, but not in their complement activation, after diet. These findings support targeting lipoproteins for the treatment of AMD.
A Professor of Ophthalmology and Associate Professor in Cell Biology with tenure at Duke University School of Medicine, Dr. Bowes Rickman is currently receiving funds as a recipient of a Research to Prevent Blindness (RPB)/International Retinal Research Foundation (IRRF) Catalyst Award for Innovative Research Approaches for AMD. The RPB/IRRF Catalyst Awards provide seed money for high-risk/high-gain vision science research, which is innovative, cutting-edge and demonstrates out-of-the box thinking. Research related to both dry and wet forms of AMD are supported by this award.
Dr. Bowes Rickman’s current studies involve the molecular mechanisms underlying the development of age-related macular degeneration, with a focus on development and studies of animal models of AMD, AMD pathogenesis and pre-clinical studies of novel therapies for AMD, and she has a strong track record of productive research in this field.
Dr. Bowes Rickman
CELL PRESS
October 31, 2019, Cell 179, 909-922
Structure of the Decorated Ciliary Doublet Microtubule
Authors: Meisheng Ma,1 Mihaela Stoyanova,2 Griffin Rademacher,3 Susan K. Dutcher,2 Alan Brown,3 and Rui Zhang,1.
1Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
2Department of Genetics, Washington University in St. Louis, MO, USA
3Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA
IN BRIEF:
Visualizing axonemal microtubules and the proteins that decorate them, on the outside and inside, points to how the underlying periodic architecture supports cilia function.
SUMMARY:
The axoneme of motile cilia is the largest macromolecular machine of eukaryotic cells. In humans, impaired axoneme function causes a range of ciliopathies. Axoneme assembly, structure, and motility require a radially arranged set of doublet microtubules, each decorated in repeating patterns with non-tubulin components. Single-particle cryo-electron microscopy is used to visualize and build an atomic model of the repeating structure of a native axonemal doublet microtubule, which reveals the identities, positions, repeat lengths, and interactions of 38 associated proteins, including 33 microtubule inner proteins (MIPs). The structure demonstrates how these proteins establish the unique architecture of doublet microtubules, maintain coherent periodicities along the axoneme, and stabilize the microtubules against the repeated mechanical stress induced by ciliary motility. This work elucidates the architectural principles that underpin the assembly of this large, repetitive eukaryotic structure and provides a molecular basis for understanding the etiology of human ciliopathies.
This study was conducted with IRRF support – Alan Brown, PhD, 2018 and 2019.
Dr. Brown is a member of the faculty of the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School in Boston. He holds a B.Sc. in Biochemistry from the University of Warwick, Coventry, UK; and a PhD in Biochemistry from the University of Cambridge, Cambridge, UK
Convening of Private Vision Research Funding Foundations
For the sixth year, Research to Prevent Blindness (RPB) organized a convening of Private Vision Research Funding Foundations with federal agencies that support vision research and vision loss prevention research and vision surveillance, as well as approve new ophthalmic drugs and devices. With a theme this year of The Eye as a Window to Overall Health, the event featured keynote presentations on the use of visual imaging to diagnose and monitor the progression of various diseases and the use of Artificial Intelligence (AI) in ophthalmology. Attendees also gave updates on collaborations between the participating foundations. International Retinal Research Foundation (IRRF) Executive Director, Sandra Blackwood attended and acted as facilitator for one of the sessions.
Collaborations That Provide Sustained Research Funding
Today’s vision scientists face many funding challenges making it imperative that all support options are available to them. Similarly, in order to ensure continued funding for young scientists who are developing their independent research projects, the IRRF must maximize every dollar. The formation of partnerships and collaborations with outstanding institutions has made it possible to accomplish this while producing a collective impact. Since 2013, New York-based Fight For Sight (FFS) and the IRRF have combined resources to provide an annual funding award: FFS – The International Retinal Research Foundation Grant-in-Aid Award that is offered and administered by FFS.
2018 — Jordan Greco, PhD, University of Connecticut, for his work in the characterization of an ion-mediated protein-based retinal implant.
Dr. Greco obtained his PhD in physical chemistry at the University of Connecticut in 2015. Under the mentorship of Dr. Robert Birge, Dr. Greco’s graduate thesis work primarily involved the investigation of the structure and function of photoactive proteins, using both spectroscopic and quantum mechanical approaches. Much of his work has contributed towards the application of the protein bacteriorhodopsin into photonic and biomimetic devices, such as protein-based optical memories and processors, photovoltaic cells, and the retinal implant developed by LambdaVision, Inc. Concurrent with his work on bacteriorhodopsin, Dr. Greco has contributed to numerous computational analyses for the excited state of behavior of heterocyclic conjugated compounds, (e.g., porphyrin, chlorins, and corroles), carotenoids (e.g., peridinin), and other polyene-based chromophores rooted in biological systems. Dr. Greco has presented this work to international audiences and he continues to remain active in the field via several multidisciplinary collaborations. (Reprinted from Crunchbase: www.crunchbase.com/person/jordan-greco)
2017 — John T. Pena, MD, PhD, Weill Cornell Medical College for his work in diabetic retinopathy.
Grant Title: Human ocular fluid contains an intercellular communication system of endogenous exosomes.
Summary: The vitreous humor of the eye is a clear gel-like structure comprised of collagen and water and fills the back of the eye.
Traditional thinking has been that the vitreous is biologically inactive. Dr. Pena’s study showed a dense organized network of extracellular vesicles (EVs) in the human vitreous. However, attempts to image vitreous EVs in whole mount or tissue sections resulted in no evidence of EVs. Yet, electron microscope (EM) studies and nano-particle tracking analysis proved that millions of EVs exist in the vitreous. To solve this discrepancy and visualize the native anatomy of vitreous EVs a hypothesis emerged that the nanometer sized EVs were lost during tissue processing secondary to reversible formalin-fixation. Therefore, this team developed an innovative fixation technique to enable visualization of vitreous EVs in situ. In addition to identifying the vitreous EVs, it was proven that vitreous EVs are a highly potent vector that can be loaded with synthetic siRNAs or proteins, and subsequently transfects retinal cells in vitro and in vivo. The team has shown that vitreous EVs can be used as a vector to efficaciously deliver therapeutic recombinant proteins to tissues like the retina and choroid.
Current and Future Academic Plans: Dr. Pena’s academic plans are to continue to grow and become a productive physician-scientist. He is currently an Assistant Professor of Ophthalmology at Weill Cornell Medicine and Principal Investigator of the laboratory. Dr. Pena plans to use his training from the clinic and basic sciences to ask pertinent questions that remain a challenge in vision research. He hopes to provide straightforward solutions that can be translated to benefit his patients and will take the next few years as an opportunity to develop strong academic relationships with his mentors and students.
Since joining the research group of Dr. Robert Birge in 2009, University of Connecticut, Jordan Greco has been actively involved in the research and development that has led to the creation of the protein-based retinal implant and the commercialization of this technology through LambdaVision. (LambdaVision is led by University of Connecticut alumni and former students in Dr. Birge’s research group, Nicole Wagner, PhD and Jordan Greco, PhD.)
Dr. Greco’s graduate thesis work influenced the design and development of the retinal implant construct and the manufacturing techniques used to produce the prosthetic. As Chief Scientific Officer, Dr. Greco is responsible for manufacturing the retinal implants and establishing standard operating procedures and quality control measures. Moreover, his research efforts helped to direct critical proof-of-concept experiments that investigated the efficacy of the retinal implant architecture.
Recently, the company’s robotic system to manufacture films that could cure blindness was brought to the International Space Station U.S. National Laboratory by the SpaceX Dragon spacecraft.
On Earth, it takes LambdaVision approximately five days for each of its three robotic stations to produce an implant. The process involves a series of alternating dipping steps, which are subject to the effects of gravity. Once complete, the process results in a membrane approximately 60 um (micrometers) thick. A micrometer is one-millionth of a meter.
In the weightless conditions of the International Space Station, LambdaVision anticipates producing a more homogeneous and stable film. If successful, Wagner and Greco anticipate they can generate a similar signal with fewer layers of protein. This would drastically decrease the time for manufacturing, and save on the cost of materials.
Dopamine D1 receptor activation contributes to light-adapted changes in retinal inhibition to rod bipolar cells
The Callahan Endowed Chair in Ophthalmology University of Alabama at Birmingham School of Medicine
Smc1 and the Cohesin Complex in Retinal Development and Disease
Proceedings of the National Academy of Sciences (PNAS) of the United States of America
CELL PRESS – Structure of the Decorated Ciliary Doublet Microtubule
Convening of Private Vision Research Funding Foundations
Collaborations That Provide Sustained Research Funding
IRRF News
Current Research News
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Contact us
For additional information or other inquiries, please write to:
The International Retinal Research Foundation, Inc.
1720 University Boulevard
Birmingham, Alabama 35233
Attn: Sandra Blackwood, MPA, Executive Director
Phone: 205-325-8103
Fax: 205-325-8394
Or by email: sblackwood@irrf.org
